Difference in Cryptococcus neoformans cellular and capsule size in sequential pulmonary and meningeal infection: a postmortem study

Cryptococcus neoformans is an encapsulated yeast that primarily causes a life-threatening meningoencephalitis in immunosuppressed individuals especially those with HIV/AIDS. Its main virulence factor is its polysaccharide capsule which interferes with complement-mediated phagocytosis. C. neoformans infections ensue following inhalation of small desiccated less encapsulated propagules leading to pulmonary pneumonia or colonization of the host's respiratory tract. Numerous murine experimental studies have shown major discrepancies in cryptococcal cell and capsule enlargement between the lung and brain. In this report, we describe a nonmurine experimental model of the striking variability between cryptococcal cell and capsule size diameters in histology sections of postmortem lung and brain in a fatal cryptococcal infection in a heart transplant recipient.     

Covert Cryptococcal Meningitis in a Patient With Systemic Lupus Erythematous

Background: Cryptococcal meningitis is a rare but well-recognized illness with a high mortality rate in immunosuppressed patients with systemic lupus erythematosus (SLE). The diagnosis of cryptococcal meningitis in these patients can be challenging, especially in the emergency department (ED), as the clinical presentation may be non-specific, which can lead to delayed treatment. Objective: To recognize risk factors associated with the development of cryptococcal meningitis infection in patients with SLE and to provide an update on the clinical presentation, prognosis, and therapeutic options. Case Report: A 21-year-old man with SLE presented with a 4-day history of headache, fever, nausea, and vomiting after being discharged from the ED 1 day before this visit, after lumbar puncture showed normal values. One week before, he had completed 7-day pulse therapy with intravenous cyclophosphamide and intravenous methylprednisone for lupus nephritis. The patient was febrile, but the remainder of the examination was normal. Laboratory data showed lymphopenia. Given his immunocompromised state, a cryptococcal antigen was added to cerebrospinal fluid (CSF) sent from the prior ED visit and was positive at a titer of 1:8. The patient was treated with amphotericin B and 5-flucytosine for 6 weeks. Ten months later the patient remained free of infection. Conclusion: Normal neurological and CSF examination do not exclude cryptococcal meningitis in immunocompromised patients with SLE. India ink or, preferably, latex agglutination test and CSF fungal culture are recommended. A high level of suspicion is the key in the diagnosis of cryptococcal meningitis and will help avoid delays in treatment.     

Immune reconstitution inflammatory syndrome after cessation of the tumor necrosis factor α blocker adalimumab in cryptococcal pneumonia

Tumor necrosis factor α antagonists have proven efficacious for a variety of autoimmune-mediated diseases. However, recent data have highlighted the risk of invasive fungal infections with their use. These agents are typically discontinued when infectious complications occur during therapy; however, the immune reconstitution inflammatory syndrome (IRIS) may be seen after drug cessation. We describe the 1st case of IRIS secondary to cryptococcal pneumonia after cessation of adalimumab.     

隐球菌荚膜抗原胶体金免疫层析法在非HIV患者隐球菌脑膜炎诊断中的价值

目的探讨隐球菌荚膜抗原胶体金免疫层析法在非HIV患者隐球菌脑膜炎中的诊断价值。方法回顾性分析2013-2018年复旦大学附属华山医院3627例疑似中枢神经系统感染的住院患者的临床资料,收集符合隐球菌脑膜炎初诊的患者214例,分析各检验结果对隐球菌脑膜炎的诊断价值。结果隐球菌脑膜炎患者多数表现为脑脊液糖和氯化物水平显著下降,蛋白含量增高,白细胞增多且以单核细胞为主,脑脊液真菌镜检和培养的阳性率分别为75.23%和78.04%,脑脊液隐球菌胶体金免疫层析法检测阳性率高达100%。隐球菌脑膜炎患者随治疗时间的推移,脑脊液和血的隐球菌荚膜抗原滴度逐渐下降。结论胶体金免疫层析法适用于非HIV患者隐球菌脑膜炎的快速诊断,灵敏度高、特异性强,对隐球菌肺炎的患者能提前筛查是否有中枢神经系统感染,对荚膜抗原的动态监测有助于隐球菌病治疗疗效的观察。     

Case Report of Cryptococcus Albidus Peritonitis in a Peritoneal Dialysis Patient and a Review of the Literature

Cryptococcus albidus is a saprophytic yeast linked to just 26 reports of human infection in the world literature. Here, we report the first case of C. albidus peritonitis, in a patient with end-stage renal disease and hepatitis C-associated cirrhosis who is on peritoneal dialysis. The patient was treated successfully with a week-long course of amphotericin B. Non-neoformans cryptococcal infections present a clinical challenge, because they are difficult to diagnose and lack established guidelines for treatment. We present a review of the literature on C. albidus infections and their treatment.     

Preventing deaths from cryptococcal meningitis: from bench to bedside

Cryptococcal meningitis (CM), a fungal disease caused by Cryptococcus spp., is the most common form of meningitis and a leading cause of death among persons with HIV/AIDS in sub-Saharan Africa. Detection of cryptococcal antigen, which is present several weeks before overt signs of meningitis develop, provides an opportunity to detect infection early. Screening persons with HIV for cryptococcal infection when they access healthcare can identify asymptomatic infected patients allowing for prompt treatment and prevention of death. A newly developed point-of-care assay for cryptococcal antigen, as well as growing evidence supporting the utility and cost-effectiveness of screening, are further reasons to consider broad implementation of cryptococcal screening in countries with a high burden of cryptococcal disease.     

Significance of cryptococcal antigen titers in patients with AIDS

We have described a patient with AIDS and cryptococcal antigen titers of 1:262,144 in CSF and 1:268,435,456 in serum. Although the prognosis is poor in AIDS patients with high cryptococcal antigen titers, this patient responded well to treatment and has been free of clinical recurrence of cryptococcal infection for 2 years.     

LA检测隐球菌荚膜多糖抗原在隐球菌性脑膜炎诊断中的应用

目的 探讨乳胶凝集试验（LA）在隐球菌性脑膜炎中的早期诊断价值.方法 收集56例确诊的隐球菌性脑膜炎患 者和25例结核性脑膜炎、病毒性脑膜炎患者的脑脊液,采用乳胶凝集试验检测隐球菌荚膜多糖抗原,并与真菌培养和直接镜检方法相比较,评价其诊断的灵敏度和特异度.结果 乳胶凝集试验、真菌培养和直接镜检3种方法诊断的灵敏度分别为91.1％、69.6％和73.2％,乳胶凝集试验特异度分别为96.0％、100％、100％.结论 乳胶凝集试验检测隐球菌荚膜多糖抗原可作为隐球菌性脑膜炎的早期诊断方法.     

Pleural involvement in cryptococcal infection

Pleural involvement of cryptococcal infection is uncommon and is more commonly observed in immunocompromised hosts than in immunocompetent ones. Pleural involvement in cryptococcal infections can manifest with or without pleural effusion. The presence of Cryptococcus spp. in the effusion or pleura is required for the diagnosis of cryptococcal pleural infection, which is commonly determined by pleural biopsy, fluid culture, and/or detection of cryptococcal antigen in the pleura or pleural fluid.     

Cryptococcal meningitis following umbilical cord blood transplantation,association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.     

The clinical laboratory evaluation of cryptococcal infections in the acquired immunodeficiency syndrome

The medical and laboratory records were reviewed in 37 acquired immunodeficiency syndrome (AIDS) patients with cryptococcal infections. In 24 patients with the presentation of cryptococcal meningitis, the initial cerebrospinal fluid (CSF) culture was positive. The initial India ink mount demonstrated organisms in 79% of culture positive CSF specimens. After therapy the subsequent India ink mounts demonstrated 84% sensitivity and 53% specificity with respect to culture outcome. Cultures of blood, bronchoalveolar lavage fluid, and brain were more likely to be positive than cultures from other sites. The initial blood cultures were positive in eight of eight patients at presentation of cryptococcal meningitis. When the initial CSF titer was greater than 1:2, the corresponding CSF culture was always positive. A negative culture during therapy did not necessarily indicate eradication of infection. The initial cerebrospinal fluid and serum cryptococcal antigen titers varied significantly and could not be correlated with survival. In three instances when the CSF cryptococcal antigen titers and cultures were negative, a positive serum cryptococcal antigen greater than 1:8 suggested disseminated infection.     

Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS.

Eight patients with AIDS were treated orally with 800 mg of fluconazole daily for cryptococcal meningitis for a mean duration of 4.5 months. Previous antifungal treatment had failed for all of the patients. No major toxicity was observed. Three patients died from cryptococcal infection. High-dose fluconazole may be effective salvage therapy for cryptococcal meningitis.     

中枢神经系统新型隐球菌性脑病的CT 分析

目的 探讨ＣＴ中在枢神经系统隐球菌感染（以下简称隐脑）诊治中的价值。方法 搜集２０例临床资料完整的隐脑ＣＴ扫描资料进行分析。结果 隐脑早期或经型病例ＣＴ表现正常,中晚期主要表现为交通性脑积水７０％,肉芽肿２５％,其它少见表现为脑内多发低密度灶、假性囊肿、弥漫性脑水肿、脑萎缩、颅内钙化灶。结论 ＣＴ检查有助于常见的化脓性及结核性脑膜炎鉴别,后者脑膜增厚与强化均非常显著且更常引起梗阻性或交通性脑积水。     

Use of cerebrospinal fluid shunt for the management of elevated intracranial pressure in a patient with active AIDS-related cryptococcal meningitis.

Persistently elevated intracranial pressure (ICP) is one of the most accurate predictors of a poor prognosis in patients with AIDS-related cryptococcal meningitis. We present a severe case of persistent cryptococcal meningitis in a patient with advanced AIDS, complicated by elevation of ICP. A ventriculoperitoneal shunt was placed that successfully lowered the ICP and alleviated the associated symptoms. The elevated ICP secondary to AIDS-related cryptococcal meningitis should be treated aggressively. Despite the risk of shunt complications, cerebrospinal fluid shunts can be considered in these patients if they do not respond to other treatment.     

系统性红斑狼疮合并隐球菌脑膜炎的诊断与治疗

目的:分析系统性红斑狼疮(SLE)合并中枢神经系统隐球菌感染的临床特点、诊断和治疗,以提高对本病的认识和诊治水平.方法:对3例SLE合并隐球菌脑膜炎(隐脑)病例的临床表现,脑脊液(CSF)变化及诊治经过进行回顾性分析.结果:SLE合并隐脑时的临床及实验室检查呈非特异性,易误诊成狼疮脑病或结核性脑膜炎(结脑),CSF涂片镜检或真菌培养发现隐球菌是确诊的关键.结论:早期诊断和有效抗真菌治疗有助于改善SLE合并隐脑患者的预后.     

A case–control study of human immunodeficiency virus-negative patients with cryptococcemia and cryptococcal meningitis in a Chinese tertiary care hospital during 10 years

ObjectiveThis study aimed to characterize patients with cryptococcemia and compare the clinical features of cryptococcemia and cryptococcal meningitis.MethodsThis was a retrospective, case–control study. We retrospectively identified blood cultures with Cryptococcus spp. growth. Controls were hospitalized patients who suffered from cryptococcal meningitis, but did not experience cryptococcemia. Controls and cases were matched by admission date, age, sex, and body weight. Clinical information was analyzed by two independent reviewers.ResultsEight patients with cryptococcemia and eight patients with cryptococcal meningitis were included. They were all negative for human immunodeficiency virus. The most common underlying disease was primary nephrotic syndrome. All patients presented with fever. The incidence of headache, nausea/vomiting, seizures, and cough/expectoration was significantly lower in patients with cryptococcemia than in those with cryptococcal meningitis. All clinical strains of Cryptococcus, except for one, were sensitive to fluconazole, voriconazole, itraconazole, amphotericin B, and flucytosine in vitro. The rate of receiving an amphotericin B-containing regimen was significantly higher in patients with cryptococcal meningitis than in those with cryptococcemia. In-hospital mortality was significantly higher in cryptococcemia cases compared with cryptococcal meningitis cases.ConclusionCryptococcemia is an unusual infection characterized by a high mortality. Cryptococcemia requires early identification and prompt antifungal therapy.     

Direct interactions of human lymphocytes with the yeast-like organism, Cryptococcus neoformans.

Lymphocytes, especially CD4+ T cells, are essential for clearance of the yeast-like organism Cryptococcus neoformans from the infected host. The mechanism(s) by which the lymphocytes facilitate elimination of cryptococci has not been elucidated. It is generally thought, however, that lymphocytes reactive with C. neoformans indirectly function by production of lymphokines to enhance clearance of the organism by natural effector cells such as macrophages. In the present study, we assessed the ability of freshly isolated human lymphocytes to interact directly with C. neoformans and to limit the growth of the organism in vitro. We found that large granular lymphocytes (LGL) as well as T cells bound to cryptococcal cells when the lymphocytes were mixed with the cryptococcal cells at a 2:1 ratio. The physical binding interactions of the two lymphocyte populations were different. LGL attached to the cryptococcal cells by many microvilli; T lymphocytes associated with the yeast through broad areas of membrane attached to the cryptococcal cell surface. The two types of lymphocyte interactions did not result in phagocytosis but resulted in direct inhibition of cryptococcal growth, making these lymphocyte interactions with cryptococci distinctly different from interactions of monocytes with cryptococci. With the human natural killer (NK) cell line, NK 3.3, we confirmed that NK cells that were present in the LGL population were capable of limiting the growth of C. neoformans. Through immunoelectron microscopy, human CD3+ lymphocytes were seen attached to cryptococcal cells and by mass cytolysis, human CD3+ lymphocytes were shown to be responsible for inhibition of C. neoformans growth. The direct inhibitory interactions of NK cells and T lymphocytes with cryptococcal cells may be important means of host defense against this ubiquitous organism that frequently causes life-threatening disease in AIDS patients.     

Successful salvage therapy of refractory HIV-related cryptococcal meningitis with the combination of liposomal amphotericin B,voriconazole, and recombinant interferon-γ

We present 2 cases of HIV-related cryptococcal meningitis, persisting after 3 and 9 months, respectively, of standard treatment. Both patients were treated successfully with a salvage regimen consisting of the combination of liposomal amphotericin B (3 mg/kg), intravenous voriconazole, and subcutaneous recombinant interferon γ-1b (200 μg thrice weekly). Voriconazole was administered at an increased dose (5 mg/kg, twice daily) to overcome interactions with co-administered ritonavir. In both patients, resolution of clinical signs and symptoms, as well as sterilization of cerebrospinal fluid cultures occurred after 10 weeks of salvage therapy. No major side effects were encountered. At the end of treatment, both patients were placed on maintenance therapy with oral fluconazole; no recurrence has been observed after 4 years of follow-up.     

Profound papilledema due to cryptococcal meningitis in acquired immunodeficiency syndrome: successful treatment with fluconazole

Although cryptococcal meningitis is a frequent infection in patients with AIDS, papilledema is rarely reported. We have reported a case of profound papilledema associated with cryptococcal meningitis in a patient with AIDS. After treatment failure with amphotericin B, the patient was successfully treated with fluconazole, and the papilledema resolved.     

Cryptococcal meningitis in patients with AIDS.

In the U.S., cryptococcal meningitis is the most common form of fungal meningitis and a major cause of morbidity and mortality among immuno-suppressed patients. In the AIDS patient, cryptococcal meningitis often presents with fever and headache and is best treated with intravenous amphotericin B and oral flucytosine, or fluconazole. However, toxic effects may result from the therapy. This disease frequently relapses necessitating life-long treatment to prevent reactivation. Essential management principles focusing upon health education are presented to promote comprehensive nursing care for patients testing positive for the human immunodeficiency virus who also have cryptococcal meningitis.